Cell surface molecules play crucial roles in lymphocyte growth control. Such molecules may function as receptors for growth-stimulating cytokines or be associated with receptors and transmit signals essential for growth regulation. Receptor blockade or removal of the stimulating cytokines can lead to decreased lymphocyte growth. For example, withdrawal of interleukins slows human lymphocyte growth and finally leads to a characteristic form of cell death called "programmed cell death" or apoptosis. E. Duvall and H. H. Wyllie, Immunol. Today 7,115 (1986). Apoptosis is the most common form of eukaryotic cell death and occurs in embryogenesis, metamorphosis, tissue atrophy, and tumor regression. A. H. Wyllie, J. F. R. Kerr, A. R. Currie, Int. Rev. Cytol. 68:251 (1980). It is also induced by cytotoxic T lymphocytes and natural killer and killer cells; by cytokines such as tumor necrosis factor (TNF) and lymphotoxin (LT); and by glucocorticoids. The characteristic signs of apoptosis are segmentation of the nucleus, condensation of the cytoplasm, membrane blebbing (zeiosis), and DNA fragmentation into multimers of about 180 base pairs (called a "DNA ladder").
Recently, it has been shown that anti-CD3 induces apoptosis of immature thymocytes in vitro. C. A. Smith et al., Nature, 337:181 (1989). It has been suggested that CD3-triggered apoptosis might be responsible for negative selection of T cells in the thymus.
The selective induction of apoptosis in cells, such as diseased cells, could prove a useful therapeutic tool.